Significance HIV infection is associated with hematologic abnormalities including decreased proliferation of hematopoietic progenitors, increased destruction of mature cells, and disturbances of regulatory cytokines. This suggests that administration of cytokines that can stimulate hematopoiesis may be useful in overcoming the abnormalities associated with infection, although there is limited evidence to suggest that such treatments are efficacious or will not enhance viral replication. Objectives Studies in adult patients suggest that only a minority of HIV-1-infected individuals carry HIV in the CD34+ hematopoietic progenitor cell compartment, and that the frequency of CD34+ infection is very low. Since fetal/neonatal hematopoietic stem cells (HSC) are known to differ from adults in their cycling rates and because they are a rapidly expanding pool, studies were conducted to assess whether early HSC populations are SIV-infected, determine if there are differences in infectivity when comparing fetuses to adults, and whether the administration of hematopoietic cytokines enhances infection. Results Bone marrow from SIV-infected fetuses, infants, and adults was sorted and cryopreserved. Two different cell populations were assessed via PCR CD34+CD38- and CD34-CD38+. PCR was performed on the lysed cells using primers for the SIV gag region. These studies have shown that the early stem cell populations are not a viral reservoir, and there is no difference in susceptibility to SIV-infection of early hematopoietic cell populations (CD34+CD38-) when comparing fetuses to infants or adults, with or without the administration of SCF+G-CSF. Thus, these findings support current evidence which suggests that the hematologic abnormalities associated with SIV/HIV infection are not the result of infection of the early stem cell population, and that the administration of hematopoietic cytokines does not alter these findings. Future Directions We will study the stromal aberrations associated with SIV-infection and assess strategies for the transplant of stem and stromal cells genetically engineered to resist infection.. KEY WORDS pregnancy, hematopoiesis, hematopoietic stem cells, fetus, SCF, G-CSF, SIV FUNDING NIH Grant HL5517